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Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity. The full effects of metformin are still poorly understood. In this study the effects of metformin on plasma xanthine oxidase (XO) activity, thiobarbituric acid-reactive substance (TBARS), lactate and fructosamine concentration as well as erythrocyte antioxidant enzyme activities were investigated in 46 patients with type 2 diabetes mellitus. All parameters were measured simultaneously just before metformin therapy (T 0 ), 1 month (T 1 ) and 2 months (T 2 ) later. Results were compared with placebo and control group. We noted significant decrease in XO activity and in TBARS concentration (p&lt;0.001) during monotherapy with metformin  vs.  placebo and T 0  group. A significant correlation was observed between the activity of XO and the concentration of fructosamine (p&lt;0.001). Erythrocyte glutathione peroxidase showed significantly lower activity in T 2  group in comparison with T 0  group (p&lt;0.01). It is known that diabetic patients produce more TBARS as a result of enhanced free radical generation the source of which may also be the large amounts of XO produced following the conversion of xanthine dehydrogenase in hypoxic diabetic tissues. Thus, our results indirectly suggest that metformin can reduce toxic tissue damage through the inhibition on XO activity.

Monotherapy with Metformin: Does It Improve Hypoxia in Type 2 Diabetic Patients?